NCT04154787

Efficacy and Safety of LNP023 Compared With Rituximab in Subjects With Idiopathic Membranous Nephropathy

A Randomized, Open-label, Two Arm, Parallel Group, Proof-of-concept Clinical Trial to Investigate the Efficacy and Safety of LNP023 Compared With Rituximab in the Treatment of Subjects With Idiopathic Membranous Nephropathy

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 37 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This was a randomized, open-label, two arm, parallel group, proof-of-concept, nonconfirmatory study evaluating the efficacy and safety of LNP023 compared with rituximab in subjects with Idiopathic (primary) membranous nephropathy (iMN) who are at high risk of disease progression defined on the basis of anti- Phospholipase A2 Receptor (PLA2R) antibody titer ≥ 60 RU/mL and proteinuria with urine protein (UP) ≥ 3.5 g/24h.

Detailed description

The overall study was planned for a total of 65 weeks and included: * A screening phase of up to 12 weeks * A treatment phase of up to 24 weeks * A post-treatment follow-up period of 29 weeks As per protocol amendment V01, subjects were randomized 1:1 to LNP023 (investigational drug) or Rituximab (comparator) and followed the below dosing schedule: * LNP023 50mg orally b.i.d. for 4 weeks followed by 200mg orally b.i.d. for 20 weeks * Rituximab 1g i.v. infusions on Day 1 and Day 15 Initially, per protocol V00, subjects were planned to be randomized in a 1:1:1 ratio to 3 treatment arms: * Low dose LNP023: LNP023 10mg orally b.i.d. for 4 weeks followed by 50mg orally b.i.d. for 20 weeks * High dose LNP023: 25mg orally b.i.d. for 4 weeks followed by 200mg orally b.i.d. for 20 weeks * Rituximab 1g i.v. infusions on Day 1 and Day 15 Following protocol amendment 1 implementation, ongoing subjects were switched to 200mg b.i.d. dose after their initial 4 weeks of treatment. 3 subjects completed treatment under protocol V00. PK/PD data from the 3 completing subjects under protocol V00 are not included in the study results. The main reason for protocol amendment V01 was to align with the clinical study results obtained from the interim analysis of ongoing phase 2 trials with LNP023 which had shown a dose dependent inhibition of the complement alternative pathway and support best efficacy results with LNP023 at a dose level of 200mg. The study was early terminated as LNP023 after interim analysis of 12 LNP023 and 14 rituximab subjects because it could already be predicted at that point that the primary goal of superiority of LNP023 vs rituximab in the reduction of UPCR at 24 weeks was not possible to achieve if the study continued to completion.

Conditions

• Idiopathic Membranous Nephropathy

Interventions

Type	Name	Description
DRUG	LNP023	Investigation of LNP023
DRUG	Rituximab	Comparison of rituximab dose

Timeline

• Start date: 2019-11-23
• Primary completion: 2023-01-20
• Completion: 2023-01-20
• First posted: 2019-11-06
• Last updated: 2024-10-09
• Results posted: 2024-07-05

Locations

18 sites across 9 countries: Argentina, China, Czechia, Germany, India, Netherlands, Spain, Taiwan, United Kingdom

Regulatory

• FDA-regulated drug study